Identification of diverse nerve growth factor-regulated genes by serial analysis of gene expression (SAGE) profiling

Neurotrophic factors such as nerve growth factor (NGF) promote a wide varie ty of responses in neurons, including differentiation. survival, plasticity , and repair. Such actions often require changes in gene expression. To ide ntify the regulated genes and thereby to more fully understand the NGF mech anism, we carried out serial analysis of gene expression (SAGE) profiling o f transcripts derived from rat PC12 cells before and after NGF-promoted neu ronal differentiation. Multiple criteria supported the reliability of the p rofile. Approximately 157,000 SAGE tags were analyzed, representing at leas t 21,000 unique transcripts. Of these, nearly 800 were regulated by 6-fold or more in response to NGF. Approximately 150 of the regulated transcripts have been matched to named genes, the majority of which were not previously known to be NGF-responsive. Functional categorization of the regulated gen es provides insight into the complex, integrated mechanism by which NGF pro motes its multiple actions. It is anticipated that as genomic sequence info rmation accrues the data derived here will continue to provide information about neurotrophic factor mechanisms.